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T‐Cell‐Derived Nanovesicles for Cancer Immunotherapy
Author(s) -
Hong Jihye,
Kang Mikyung,
Jung Mungyo,
Lee Yun Young,
Cho Yongbum,
Kim Cheesue,
Song Seuk Young,
Park Chun Gwon,
Doh Junsang,
Kim ByungSoo
Publication year - 2021
Publication title -
advanced materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 10.707
H-Index - 527
eISSN - 1521-4095
pISSN - 0935-9648
DOI - 10.1002/adma.202101110
Subject(s) - granzyme , cytotoxic t cell , immunotherapy , granzyme b , cancer research , tumor microenvironment , cancer immunotherapy , cancer cell , immunogenic cell death , t cell , materials science , cancer , perforin , cd8 , immunology , immune system , medicine , biology , tumor cells , biochemistry , in vitro
Although T‐cell therapy is a remarkable breakthrough in cancer immunotherapy, the therapeutic efficacy is limited for solid tumors. A major cause of the low efficacy is T‐cell exhaustion by immunosuppressive mechanisms of solid tumors, which are mainly mediated by programmed death‐ligand 1 (PD‐L1) and transforming growth factor‐beta (TGF‐β). Herein, T‐cell‐derived nanovesicles (TCNVs) produced by the serial extrusion of cytotoxic T cells through membranes with micro‐/nanosized pores that inhibit T‐cell exhaustion and exhibit antitumoral activity maintained in the immunosuppressive tumor microenvironment (TME) are presented. TCNVs, which have programmed cell death protein 1 and TGF‐β receptor on their surface, block PD‐L1 on cancer cells and scavenge TGF‐β in the immunosuppressive TME, thereby preventing cytotoxic‐T‐cell exhaustion. In addition, TCNVs directly kill cancer cells via granzyme B delivery. TCNVs successfully suppress tumor growth in syngeneic‐solid‐tumor‐bearing mice. Taken together, TCNV offers an effective cancer immunotherapy strategy to overcome the tumor's immunosuppressive mechanisms.